Proposed is the study of hyperthermic patients to: I. Characterize specific aspects of protein, carbohydrate and fat metabolism by: A. Indirect, online calorimetric computation of total heat output, oxygen consumption, respiratory quotient, and quantitative consumption studies. B. Quantitation of total body and skeletal muscle protein catabolism by determination of urea production rate and 3-methylhistidine excretion. C. Measurement of the rate of glucoenogenesis by infusion of C14 alanine and H3 glucose and radioassay of serum activities. D. Determination of free fatty acid turnover rates by infusion of C14 labeled oleate and determination of serum activity. E. By radioimmunoassay of circulating levels of the regulatory hormones-insulin, catecholamines and glucagon. II. Determine the FLUX of water and critical ions by balance studies of phosphorus, magnesium, calcium, sodium, potassium and water. III. Investigate immunologic function before, during and after hyperthermia by: A. Characterizaton of T and B cell immune functions 1. skin test, 2. E rosette, 3. EAC rosette, 4. lymphocyte proliferation, 5. migration inhibition factors. B. Quantitation of peripheral blood leukocyte function. 1. chemototactic response 2. phagocytic bactericidal activity. IV. Support hyperthermic treatments of prolonged duration by providing around-the-clock laboratory assessment of critical substances such as PO4--, Mg ions, lactic acid, Ca ions which are not available from hospital labs on an immediate or stat basis. V. Also proposed is to explore, using a canine model, metabolic manipulations postulated to increase mammalian tolerance of hyperthermia. The first year effort will focus on the use of induced ketosis for induction of lipid-consuming energy production pathways in central nervous system tissue as a means to increase the magnitude and duration of hyperthermia tolerable by animals and ultimately man.